795 A multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A843-A843
Author(s):  
Michael Wagner ◽  
Megan Othus ◽  
Sandip Patel ◽  
Christopher Ryan ◽  
Ashish Sangal ◽  
...  
Keyword(s):  
Phase Ii ◽  
Immune Checkpoint ◽  
Uv Light ◽  
Light Exposure ◽  
Case Reports ◽  
Objective Response ◽  
Open Label ◽  
Primary Tumors ◽  
Multicenter Phase ◽  
Grade 3

BackgroundAngiosarcoma is a rare cancer of endothelial cells that can be aggressive and carries a high mortality. A subset of angiosarcomas are characterized by high tumor mutational burden (TMB) and UV light exposure DNA mutational signature. Isolated case reports have suggested clinical efficacy of immune checkpoint blockade in angiosarcoma; no prospective studies of immune checkpoint inhibition in angiosarcoma have been reported. We report efficacy analysis results for patients with advanced or unresectable angiosarcoma treated with ipilimumab and nivolumab as a cohort of an ongoing phase II study for rare cancers (NCT02834013).MethodsThis is a prospective, open-label, multicenter phase II clinical trial of ipilimumab (1mg/kg IV q6weeks) plus nivolumab (240mg IV q2weeks) for patients with metastatic or unresectable angiosarcoma. Primary endpoint is objective response rate as assessed by RECIST v1.1, including measurable cutaneous disease that can be followed by photography. Secondary endpoints include PFS, OS, stable disease at six months, and toxicity. A two-stage design is used with six patients in the first stage and an additional ten patients in the second stage.ResultsAt data cutoff, 16 patients with angiosarcoma were enrolled. Median age was 68 years (25-81 years). Median number of prior lines of therapy was 2 (0-5). 9 patients had cutaneous primary tumors of any cutaneous site, 7 had non-cutaneous primary tumors. ORR for all patients was 25% (4/16, table 1, figure 1). Subgroup analysis revealed that 60% (3/5) of patients with primary cutaneous tumors of the scalp or face had a confirmed objective response. 6-month PFS was 38%. 75% of patients experienced an adverse event (AE), and 25% experienced a grade 3-4 AE. 68.8% experienced an immune related AE (irAE), and 2 (12.5%) developed grade 3 or 4 irAEs. Grade 3-4 irAEs were ALT and AST increase and diarrhea. There were no grade 5 toxicities.ConclusionsThe combination of ipilimumab and nivolumab was well tolerated and had an ORR of 25% in angiosarcoma regardless of primary site, with 3 of 5 patients with cutaneous tumors of the scalp or face responding. Ipilimumab and nivolumab warrant further investigation in angiosarcoma.AcknowledgementsFunding: National Institutes of Health/National Cancer Institute grant awards CA180888, CA180819, CA180868; and in part by Bristol-Myers Squibb CompanyTrial RegistrationNCT02834013Ethics ApprovalThis study was approved by the NCI CIRB.

scholarly journals Multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART)

2021 ◽  
Vol 9 (8) ◽  
pp. e002990
Author(s):  
Michael J Wagner ◽  
Megan Othus ◽  
Sandip P Patel ◽  
Chris Ryan ◽  
Ashish Sangal ◽  
...  
Keyword(s):  
Phase Ii ◽  
Cell Cancer ◽  
Objective Response ◽  
Median Number ◽  
Open Label ◽  
Primary Tumors ◽  
Multicenter Phase ◽  
Mutation Burden ◽  
Registration Number ◽  
Grade 3

PurposeAngiosarcoma is a rare aggressive endothelial cell cancer with high mortality. Isolated reports suggest immune checkpoint inhibition efficacy in angiosarcoma, but no prospective studies have been published. We report results for angiosarcoma treated with ipilimumab and nivolumab as a cohort of an ongoing rare cancer study.MethodsThis is a prospective, open-label, multicenter phase II clinical trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) for metastatic or unresectable angiosarcoma. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints include progression-free (PFS) and overall survival, and toxicity. A two-stage design was used.ResultsOverall, there were 16 evaluable patients. Median age was 68 years (range, 25–81); median number of prior lines of therapy, 2. Nine patients had cutaneous and seven non-cutaneous primary tumors. ORR was 25% (4/16). Sixty per cent of patients (3/5) with primary cutaneous scalp or face tumors attained a confirmed response. Six-month PFS was 38%. Altogether, 75% of patients experienced an adverse event (AE) (at least possibly related to drug) (25% grade 3–4 AE); 68.8%, an immune-related AE (irAE) (2 (12.5%), grade 3 or 4 irAEs (alanine aminotransferase/aspartate aminotransferase increase and diarrhea)). There were no grade 5 toxicities. One of seven patients in whom tumor mutation burden (TMB) was assessed showed a high TMB (24 mutations/mb); that patient achieved a partial response (PR). Two of three patients with PDL1 immunohistochemistry assessed had high PDL1 expression; one achieved a PR.ConclusionThe combination of ipilimumab and nivolumab demonstrated an ORR of 25% in angiosarcoma, with three of five patients with cutaneous tumors of the scalp or face responding. Ipilimumab and nivolumab warrant further investigation in angiosarcoma.Trial registration numberNCT02834013.

scholarly journals Pyrotinib in HER2-Mutant Advanced Lung Adenocarcinoma After Platinum-Based Chemotherapy: A Multicenter, Open-Label, Single-Arm, Phase II Study

2020 ◽  
Vol 38 (24) ◽  
pp. 2753-2761 ◽  
Author(s):  
Caicun Zhou ◽  
Xingya Li ◽  
Qiming Wang ◽  
Guanghui Gao ◽  
Yiping Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Unmet Need ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Grade 3

PURPOSE Targeted therapies against non–small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of pyrotinib in patients with HER2-mutant advanced NSCLC in a prospective, multicenter, open-label, single-arm, phase II study. PATIENTS AND METHODS Patients with stage IIIB or IV HER2-mutant lung adenocarcinoma who were previously treated with platinum-based chemotherapy were enrolled to receive pyrotinib at a dose of 400 mg/d for 21-day cycles. The primary end point was objective response rate per independent review committee (IRC). RESULTS Between October 20, 2016, and December 10, 2018, 60 patients received pyrotinib monotherapy. At baseline, 58 (96.7%) were stage IV, and 25 (41.7%) received at least 2 lines of prior chemotherapy. As of data cutoff on June 20, 2019, IRC-assessed objective response rate was 30.0% (95% CI, 18.8% to 43.2%). All subgroups of patients with different HER2 mutation types showed a favorable objective response rate. The objective response rates were similar between patients with and without brain metastases (25.0% v 31.3%). The median duration of response was 6.9 months (95% CI, 4.9 to 11.1 months). The median progression-free survival was 6.9 months (95% CI, 5.5 to 8.3 months) per IRC. The median overall survival was 14.4 months (95% CI, 12.3 to 21.3 months). Treatment-related adverse events of grade 3 or 4 occurred in 28.3% of patients, with the most common being diarrhea (20.0%; all grade 3). No treatment-related deaths were reported. CONCLUSION Pyrotinib showed promising antitumor activity and an acceptable safety profile in chemotherapy-treated patients with HER2-mutant NSCLC.

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

scholarly journals Pimasertib Versus Dacarbazine in Patients With Unresectable NRAS-Mutated Cutaneous Melanoma: Phase II, Randomized, Controlled Trial with Crossover

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1727 ◽  
Author(s):  
Celeste Lebbé ◽  
Caroline Dutriaux ◽  
Thierry Lesimple ◽  
Willem Kruit ◽  
Joseph Kerger ◽  
...  
Keyword(s):  
Phase Ii ◽  
Cutaneous Melanoma ◽  
Controlled Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Serious Adverse Events ◽  
Unresectable Stage ◽  
Secondary Endpoints ◽  
Grade 3

This study investigated the efficacy and safety of pimasertib (MEK1/MEK2 inhibitor) versus dacarbazine (DTIC) in patients with untreated NRAS-mutated melanoma. Phase II, multicenter, open-label trial. Patients with unresectable, stage IIIc/IVM1 NRAS-mutated cutaneous melanoma were randomized 2:1 to pimasertib (60 mg; oral twice-daily) or DTIC (1000 mg/m2; intravenously) on Day 1 of each 21-day cycle. Patients progressing on DTIC could crossover to pimasertib. Primary endpoint: investigator-assessed progression-free survival (PFS); secondary endpoints: overall survival (OS), objective response rate (ORR), quality of life (QoL), and safety. Overall, 194 patients were randomized (pimasertib n = 130, DTIC n = 64), and 191 received treatment (pimasertib n = 130, DTIC n = 61). PFS was significantly improved with pimasertib versus DTIC (median 13 versus 7 weeks, respectively; hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.42–0.83; p = 0.0022). ORR was improved with pimasertib (odds ratio 2.24, 95% CI 1.00–4.98; p = 0.0453). OS was similar between treatments (median 9 versus 11 months, respectively; HR 0.89, 95% CI 0.61–1.30); 64% of patients receiving DTIC crossed over to pimasertib. Serious adverse events (AEs) were more frequent for pimasertib (57%) than DTIC (20%). The most common treatment-emergent AEs were diarrhea (82%) and blood creatine phosphokinase (CPK) increase (68%) for pimasertib, and nausea (41%) and fatigue (38%) for DTIC. Most frequent grade ≥3 AEs were CPK increase (34%) for pimasertib and neutropenia (15%) for DTIC. Mean QoL scores (baseline and last assessment) were similar between treatments. Pimasertib has activity in NRAS-mutated cutaneous melanoma and a safety profile consistent with known toxicities of MEK inhibitors. Trial registration: ClinicalTrials.gov, NCT01693068.

Natural history of diarrhea associated with the anti-CTLA4 monoclonal antibody CP-675,206

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3038-3038 ◽  
Author(s):  
S. Antonia ◽  
J. Sosman ◽  
J. M. Kirkwood ◽  
B. Redman ◽  
T. F. Gajewski ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Dose Range ◽  
Objective Response ◽  
Stage Iv ◽  
Open Label ◽  
Similar Frequency ◽  
Severe Diarrhea ◽  
Grade 3 ◽  
Stage Iv Melanoma

3038 Background: Diarrhea resulting from immune activation has been associated with CTLA4 blockade. For example, in patients (pts) with stage IV melanoma receiving ipilimumab (MDX-010), a number of pts developed grade 3/4 autoimmune enterocolitis and severe diarrhea (Attia et al, 2005). In a single-dose phase I trial of CP-675,206 at doses up to 15 mg/kg in pts with solid tumors (n = 39), 9 instances of diarrhea were reported including 3 grade 3 events (Ribas et al, 2005). The incidence and severity of diarrhea was assessed in pts receiving CP- 675,206 in a large phase I/II study. Methods: An open-label phase I/II trial of CP-675,206 was conducted in pts with stage III (unresectable) or stage IV melanoma and an ECOG PS = 1. Diarrhea was assessed in pts treated at the phase II doses: 10 mg/kg monthly (Q1M) in phase I (n = 22), or 10 mg/kg Q1M (n = 44) or 15 mg/kg every 3 months (Q3M, n = 45) in phase II. Results: Medians of 3.5 doses (range, 1 to 18) at 10 mg/kg Q1M in phase I, 3 doses (range, 1 to 26) at 10 mg/kg Q1M in phase II, and 1 dose (range, 1 to 9) at 15 mg/kg Q3M were administered with 100% dose compliance. Treatment-related diarrhea was reported by 43 (39%) of 111 pts, and grade 3 diarrhea occurred in 14 (13%) pts. One patient had grade 4 colitis resulting in a colectomy. Diarrhea (all grades) occurred with similar frequency in each dose group; however, grade 3 treatment-related diarrhea occurred in 8% of pts treated with 15 mg/kg Q3M compared with 18% of pts treated with 10 mg/kg Q1M in phase I and 14% of pts treated with 10 mg/kg Q1M in phase II. Among 9 pts with an objective response, 8 experienced diarrhea (3 of which were grade 3). The majority of cases (65%) were mild to moderate in severity with a median time to onset of 51 days (range, 1 to 583 days) and resolution of 8 days (range, 1 to 182 days). More than half of pts who reported serious events of diarrhea were treated with steroids. Conclusions: Diarrhea associated with CP-675,206 was primarily mild to moderate in severity, transient, and manageable. In addition, 15 mg/kg Q3M may be better tolerated than 10 mg/kg Q1M. Ongoing clinical trials in pts with advanced melanoma will provide further information about the incidence, severity, and optimal management of diarrhea associated with CP-675,206. No significant financial relationships to disclose.

Oxaliplatin, irinotecan, and cetuximab in advanced gastric cancer. First efficacy results of a multicenter phase II trial (AGMT Gastric-2) of the Arbeitsgemeinschaft Medikamentoese Tumortherapie (AGMT)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4538-4538
Author(s):  
E. Woell ◽  
R. Greil ◽  
W. Eisterer ◽  
M. Fridrik ◽  
B. Grünberger ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Multicenter Phase ◽  
Grade 3 ◽  
Line Setting

4538 Background: Patients (pts.) suffering from advanced gastric cancer have still a poor prognosis and treatment options are limited. In our previous phase II trial (AGMT-Gastric-1) we could show that the combination of oxaliplatin and irinotecan was well tolerated and showed an objective response rate of 58% (Anticancer Res 28:2901–2906, 2008). This chemotherapy regimen was tested in combination with cetuximab in a multicenter phase II trial. Methods: Oxaliplatin 85 mg/m2 biweekly and irinotecan 125 mg/m2 biweekly were combined with cetuximab 400 mg/m2 loading dose and subsequently weekly 250 mg/m2. 51 patients with histological proven unresectable and/or metastatic gastric adenocarcinoma were treated in a first line setting. Median age: 62 years (range 19–79 years), PS 0: 25 patients, PS 1+2 26 patients, single metastatic site: 24 patients, multiple metastases: 27 patients. Results: Frequently reported adverse events (more than 20% of pts.) were predominantly grade 1 or 2 and included neutropenia (35% of pts.), thrombocytopenia (33%), anemia (73%), nausea (45%), diarrhea (57%), alopecia (22%), and fatigue (37%). Grade 3 and 4 toxicities included neutropenia in 9/1 pts., thrombocytopenia in 1/0 pts., anemia in 3/1 pts., nausea in 2/0 pts., and diarrhea in 7/2 pts. Sensory neuropathy occurred mostly as grade 1 and 2 in 37% of pts., in 7 pts. grade 3 neurotoxicity was observed. Acneiform skin rash grade 1 / 2 / 3 / 4 was reported in 31% / 20% / 6% / 2% of pts. respectively. 16 pts. went off-study due to neutropenia (n=5), nausea/vomiting (n=1), diarrhea (n=1), progressive disease (n=3), toxic colon (n=2), and allergic reaction to cetuximab at first (n=2), second (n=1) or third infusion (n=1). 35 patients are assessable for response with 1 pt. (3%) showing a CR, 21 pts. (60%) a PR, 7 pts. (20%) a SD and PD in 6 pts. (17%). A disease control rate was achieved in 83%. Median time to progression was 24.8 weeks (n=29), median overall survival 38.1 weeks (n=32). Conclusions: The combination of oxaliplatin and irinotecan with cetuximab is feasible, safe and active in advanced gastric cancer. [Table: see text]

Anlotinib and irinotecan for advanced Ewing sarcoma after failure of standard therapy: A multicenter, two-cohort, single-arm, open label, phase Ib/II trial (NCT03416517).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11012-11012
Author(s):  
Jie Xu ◽  
Lu Xie ◽  
Wei Guo ◽  
Xiaodong Tang ◽  
Rongli Yang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Ewing Sarcoma ◽  
Initial Level ◽  
Objective Response ◽  
Complete Response ◽  
Fixed Dose ◽  
Open Label ◽  
Phase Ib ◽  
Open Label Phase ◽  
Grade 3

11012 Background: Both protracted irinotecan and anti-angiogenesis therapy have shown promising results in Ewing sarcoma. We did this phase Ib/II trial to first define the proper dose of irinotecan in combination with anlotinib in Ewing sarcoma and then evaluate efficacy. Methods: Patients diagnosed with recurrent or refractory Ewing sarcoma were enrolled and sub-classified into cohort A (≥16y) or cohort B ( < 16y). In the dose-defining phase Ib portion, anlotinib was given at a fixed dose of 12mg D1-14every 21 days, while the de-escalated 3+3 design was used to detect the recommended dose of irinotecan in each cohort from an initial level of 20mg/m2/d dx5x2. Recommended phase 2 dose (RP2D) was defined as the highest dose at which no more than 30% patients experience a DLT in the first two courses. In the next dose-expanding phase II portion, the primary endpoint was objective response rate at 12 weeks (ORR12w). A conventional two-stage study design model was used. Results: 41 patients were enrolled with 29 in cohort A and 12 in cohort B. For cohort A, first 5 patients were treated at initial level in phase Ib portion, two of whom subsequently experienced delayed diarrhea as dose-limiting toxicity (DLT). Additional six patients were then treated at a lower dose of 15mg/m2. Since no more DLT was recorded, it was used as RP2D. 23/24 patients in cohort A phase II were available for response evaluation at 12 weeks, with one complete response (CR), 14 partial response (PR) (including one CMR who has a negative PET/CT scan but still abnormal lesions in MR scan), 2 stable disease (SD) and 6 progressive disease (PD). ORR12wwas 62.5%. For cohort B, no DLT was noticed in the first six patients treated at the initial level which was used as RP2D later. Finally, 12 patients were included in cohort B. ORR12wwas 83.3% with two CR, 8 PR (including one CMR) and two PD. Although effective, cohort B were closed because of slow enrollment. Most common grade 3/4 adverse events were diarrhea, abdominal pain and neutropenia. The genotype of UGT1A1*1 and UGT1A1*28 were not associated with the risk of diarrhea. Conclusions: The combination of irinotecan and anlotinib demonstrated an acceptable toxicity profile with promising evidence of clinical efficacy in advanced Ewing sarcoma. Clinical trial information: NCT03416517.

Phase II study of the combination of abemaciclib and pembrolizumab in locally advanced unresectable or metastatic gastroesophageal adenocarcinoma: Big Ten Cancer Research Consortium BTCRC-GI18-149.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS461-TPS461
Author(s):  
Nataliya Volodymyrivna Uboha ◽  
Jens C. Eickhoff ◽  
Chandrikha Chandrasekharan ◽  
Shadia Ibrahim Jalal ◽  
Al Bowen Benson ◽  
...  
Keyword(s):  
Phase Ii ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Locally Advanced ◽  
Open Label ◽  
Significance Level ◽  
Gastroesophageal Adenocarcinoma

TPS461 Background: Metastatic gastroesophageal adenocarcinoma (GEA) has poor prognosis. Overall survival (OS) remains around 12 months (mo) with current therapies. Pembrolizumab is approved for advanced GEA that has progressed on at least 2 prior lines of systemic therapy. However, the majority of patients progress on this treatment, and less than 15% of patients experience objective response (OR). This study will evaluate efficacy of pembrolizumab in combination with cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, abemaciclib, in patients with advanced GEA. Preclinical studies have demonstrated that CDK4/6 inhibitors can increase anti-tumor immunity and can synergize with immune checkpoint inhibitors. Based on these data, we hypothesize that abemaciclib will augment response to pembrolizumab in GEA. Methods: This is a multi-institutional, single arm, open label, phase II study of abemaciclib in combination with pembrolizumab in patients with advanced GEA who have progressed or were intolerant to at least 2 prior lines of therapy. Patients previously treated with immune checkpoint inhibitors or with microsattelite unstable tumors will be excluded. Treatments will be given on a 21 day cycle until disease progression or intolerable toxicities. Pembrolizumab, 200 mg intravenously, will be given on day 1, and abemaciclib, 150 mg, will be taken orally twice a day on days 1-21. Primary endpoint is progression free survival (PFS). Secondary endpoints include PFS rate at 6 mo, disease control rate, OS and OR rate. Correlative endpoints will examine relationship between PDL1 status, genomic signature and treatment response. Saliva samples will be collected for microbiome analysis. Archival tumor tissue and blood samples will be banked for future studies. A total of 31 evaluable subjects will be enrolled to detect an anticipated increase in the median PFS from 2 months (null hypothesis) to 4 months with 80% power at the one-sided 0.05 significance level. The trial is open to enrollment. Clinical trial information: NCT03997448.

A phase II open-label study of cabozantinib after first-line treatment including an immune-checkpoint combination in patients with advanced or unresectable renal cell carcinoma: The BREAKPOINT trial (MeetUro trial 03 - EudraCT number 2018-000582-36).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 326-326
Author(s):  
Giuseppe Procopio ◽  
Chiara Pircher ◽  
Melanie Claps ◽  
Valentina Guadalupi ◽  
Alessia Mennitto ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
First Line ◽  
Open Label

326 Background: Antiangiogenic therapy has been a milestone in the treatment of metastatic renal cell carcinoma (mRCC) for years. The positive results with immune-checkpoint inhibitors (ICI) are changing the frontline standard of care of mRCC patients (pts). To date, prospective data are lacking to determine the efficacy of antiangiogenic therapy in pts progressed to ICI. The multikinase inhibitor Cabozantinib (cabo) has shown prolonged survival in pre-treated mRCC pts. Moreover, by targeting multiple pathways and crucial kinases involved in microenvironment-driven immune-escape, it may represent an ideal agent to be used sequentially after ICI. Methods: This is the first prospective open label, single arm, multicenter, phase II study to evaluate efficacy and safety of Cabo in pts with mRCC pre-treated with adjuvant or first line PD-1/PD-L1-based therapy (as monotherapy or in combination with an TKI or anti CTLA-4). Cabo 60 mg once daily was administered until progressive disease (PD) or unacceptable toxicity. The primary endpoint was progression free survival (PFS), secondary endpoints were overall survival (OS), objective response rate (ORR) and safety. Results: Among 23 patients enrolled, 22 were included in the analysis (one was excluded for screening failure). Median age was 59.5 years (range: 29-74), 69.5% were male. At baseline, Karnofsky performance status was 100 in 59% of pts, 80-90 in 31.8% and 70-80 in 9%. 22.7% of pts had a good Heng score, 50% intermediate and 27.2% poor. Median duration of the previous therapy with anti PD-1 or anti-PD-L1 compounds was 4.3 months. Pts received an average of 4.7 months of Cabo. Among evaluable cases, 6 pts (27.2%) achieved a partial response and 5 pts (22.7%) stable disease. The median follow-up was 7.2 months and the median PFS was 7.2 months. 2 pts discontinued treatment for toxicity, 8 pts for PD, 1 patient discontinued treatment for different reason than PD, 11 pts are still on treatment. Grade (G) 3 adverse events (AEs) occurred in 22.7% of pts; the most common AEs were hand and foot syndrome (HFS) (G1 in 36.3% of pts, G2 18.1%, G3 4.5%), diarrhea (G1 31.8%, G2 18.1%), hypothyroidism (G1 9.09 %, G2 22.7 %), mucositis (G1 36.3%, G2 4,5%), and fatigue (G1 18.1%, G2 18.1%). Transitory withholding of cabo was observed in 63.6% of pts (14/22) and it was due to AEs in the 90% of the cases. For 5/22 pts (22.7 %), dose reduction was needed to manage AEs. The most common AEs leading to temporary drug interruption were HFS G1-3 (13.9%), liver disfunction G1-G2 (13.9%), diarrhea G1-G2 (11.6%), nausea and vomiting G2 (11.6 %) and fatigue G2 (9.3%). Conclusions: So far, the treatment with cabo after a I line anti-PD-1 based immunotherapy resulted active and well tolerated. Clinical trial information: NCT03463681 .

scholarly journals Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial

2020 ◽  
Vol 38 (34) ◽  
pp. 4095-4106
Author(s):  
Chunyan Lan ◽  
Jingxian Shen ◽  
Yin Wang ◽  
Jundong Li ◽  
Zhimin Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Advanced Cervical Cancer ◽  
Open Label ◽  
Duration Of Response ◽  
Grade 3

PURPOSE Camrelizumab is an antibody against programmed death protein 1. We assessed the activity and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, in patients with advanced cervical cancer. METHODS This multicenter, open-label, single-arm, phase II study enrolled patients with advanced cervical cancer who progressed after at least one line of systemic therapy. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once per day. The primary end point was objective response rate (ORR) assessed by investigators per RECIST version 1.1. Key secondary end points were progression-free survival (PFS), overall survival (OS), duration of response, and safety. RESULTS Forty-five patients were enrolled and received treatment. Median age was 51.0 years (range, 33-67 years), and 57.8% of patients had previously received two or more lines of chemotherapy for recurrent or metastatic disease. Ten patients (22.2%) had received bevacizumab. Median follow-up was 11.3 months (range, 1.0-15.5 months). ORR was 55.6% (95% CI, 40.0% to 70.4%), with two complete and 23 partial responses. Median PFS was 8.8 months (95% CI, 5.6 months to not estimable). Median duration of response and median OS were not reached. Treatment-related grade 3 or 4 adverse events (AEs) occurred in 71.1% of patients, and the most common AEs were hypertension (24.4%), anemia (20.0%), and fatigue (15.6%). The most common potential immune-related AEs included grade 1-2 hypothyroidism (22.2%) and reactive cutaneous capillary endothelial proliferation (8.9%). CONCLUSION Camrelizumab plus apatinib had promising antitumor activity and manageable toxicities in patients with advanced cervical cancer. Larger randomized controlled trials are warranted to validate our findings.

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